7-55939293-C-G

Variant names:

• chr7-55939293-C-G
• rs1786415933
• NM_182633.3:c.619C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182633.3(ZNF713):​c.619C>G​(p.Leu207Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: ZNF713 NM_182633.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0370

Genes affected

ZNF713 (HGNC:22043): (zinc finger protein 713) The protein encoded by this gene contains C2H2 zinc finger domains. In some individuals, a CGG-repeat expansion from 5-22 repeats to 68-450 repeats has been identified in the first intron of this gene. This mutation is thought to effect the expression of this gene and it has been proposed that it may be associated with Autistic Spectrum Disorder. [provided by RefSeq, Jul 2016]

ENSG00000249773 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062143356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF713	NM_182633.3	c.619C>G	p.Leu207Val	missense_variant	Exon 7 of 7	ENST00000429591.4	NP_872439.2
ZNF713	NM_001366796.2	c.580C>G	p.Leu194Val	missense_variant	Exon 7 of 7		NP_001353725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF713	ENST00000429591.4	c.619C>G	p.Leu207Val	missense_variant	Exon 7 of 7	5	NM_182633.3	ENSP00000416662.3
ENSG00000249773	ENST00000426595.1	c.269-13886C>G		intron_variant	Intron 6 of 7	5		ENSP00000390331.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74340

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 03, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.580C>G (p.L194V) alteration is located in exon 4 (coding exon 4) of the ZNF713 gene. This alteration results from a C to G substitution at nucleotide position 580, causing the leucine (L) at amino acid position 194 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.50
DEOGEN2	Benign	0.035	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.12	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.96	.;L
PrimateAI	Benign	0.22	T
REVEL	Benign	0.060
Sift4G	Benign	0.49	T;T
Polyphen		0.16	.;B
Vest4		0.028
MutPred		0.56		.;Loss of catalytic residue at L194 (P = 0.1089);
MVP		0.53
MPC		0.16
ClinPred		0.047	T
GERP RS		-4.6
Varity_R		0.042
gMVP		0.022

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1786415933; hg19: chr7-56006986;